What’s in a voxel?

Researchers have several ways to peer into the human brain. A commonly-used tool is magnetic resonance imaging (MRI) and unlike the two-dimensional pixels in photography, voxels are used to describe the volume of brain measured by MRI. Currently, the standard voxel is a of ~1mm, about the size of coarse sea salt. Combining millions of voxels produces the 3D image of the brain you see in the figure. The view of the brain at this high resolution has led to some common ideas about the ‘autism’ brain.

Cynthia Schumann, Ph.D. and Christine Nordahl, Ph.D. of the MIND Institute at UC Davis, show how imaging, when paired with the microscopic inspection of the post mortem human brain, can help answer questions about typical and disordered brain development. MRI studies of autism have revealed an atypical trajectory of brain growth during early childhood, characterized by brain overgrowth, that is present especially in the frontal cortex (involved in higher mental functions) and also in specific structures such as the amygdala (involved in memory functions, particularly of emotional experiences).

Why are these areas growing larger than normal in young children? One way to answer this question is to look at the cells in these enlarged areas. That solution requires samples of donated postmortem brain tissue.

To give an idea of what’s in a voxel in a typical 3 year old child’s brain: there are an estimated 40,000 neurons in the space of a voxel in the cortex and 7000 in each voxel in the amygdala. The pictures in row C show just a portion of cells in a single voxel in the brain areas indicated. Some evidence indicates that neurons and another cell type called glia are more abundant in the brains of individuals with autism. Connections between cells need space and the more numerous brain cell branching that has been found can also lead to a size increase of a given area.

In addition to counting cells and their connections, fine-scale anatomy allows us to examine the layered organization of cells in the cerebral cortex and other local relationships in different brain areas. When researchers observe cells that are “out of place”, this suggests differences in the functioning of that local network of cells.

Researchers can also use antibodies to localize various molecules in post-mortem brain tissue. With these techniques scientists can identify cells that carry a particular type of neurotransmitter, or other cellular signals. One can also extract and analyze the building blocks for proteins in RNA and DNA and look for regions where a certain gene may have been “turned on” or off more than expected.

Given the coarse resolution of MRI, the field must look towards post-mortem human brain research to help us understand the neurobiological underpinnings of the difference in brain growth patterns that have been found in MRI studies. MRI studies are very helpful in targeting which brain regions should be explored further in post-mortem studies.

Autism Speaks’ Autism Tissue Program supports specialized neuropathology research by providing approved scientists access to the most rare and necessary of resources, post mortem human brain tissue. We wish to recognize the commitment and generosity by our ATP donor families. More information can be found at www.autismtissueprogram.org or call 877-333-0999 for information or to initiate a brain donation.

Brain Research will be publishing a special issue of articles that feature presentations at the 2010 Brain Research meeting. Dr. Schumann’s paper is currently available online with appropriate institutional access or for purchase.

Schumann, CM and CW Nordahl. Bridging the gap between MRI and postmortem research in autism. Brain Res. (2010), doi:10.1016/j.brainres.2010.09.061.